Sudden infant death syndrome (SIDS) is a leading cause of infant mortality with incidence of about 0.8/1000 live births in the U.S. and considerably higher rates in at-risk populations, including Native Americans and the Cape Coloured (mixed ancestry) community in South Africa. A recent study has implicated prenatal alcohol exposure as an important risk factor for SIDS that warrants further investigation. It has been hypothesized that medullary serotonergic network deficits may be responsible, in part, for some SIDS deaths. For the past 5 years, we have been conducting a prospective, longitudinal study on the effects of prenatal alcohol exposure in the Cape Coloured community in collaboration with researchers from the University of Cape Town School of Medicine. This research has demonstrated our ability to recruit mothers from this community; obtain valid assessments of FAS, prenatal alcohol exposure, maternal alcoholism, smoking and depression, and socioenvironmental and medical risk; and perform state-of-the-art infant neurobehavioral assessments with Cape Town infants. We have found an exceptionally high rate of alcohol abuse and dependence among pregnant women in this population and of FAS among their infants. The high incidence of both SIDS and FAS in this large metropolitan area, the readily accessible maternal heavy drinking population, and our established, productive research collaboration make Cape Town uniquely appropriate as a Comprehensive Clinical Site. The proposed cooperative agreement would expand our ongoing collaboration to include researchers in pathology and obstetrics. The aims are (1) to conduct an assessment of the incidence of SIDS and stillbirths in Cape Town, using contemporary diagnostic criteria and procedures, including neuropathological examinations of SIDS victims and controls; (2) to test the hypothesis that prenatal binge drinking increases the risk of SIDS and to evaluate that risk in relation to risks associated with prenatal maternal smoking, preterm birth, infant gender and sleeping position, seasonal variation, parental education, and maternal depression; (3) to test the hypothesis that certain moderator variables-- years of drinking, severity of maternal alcohol abuse and dependence, lower maternal weight and prenatal smoking, and the absence of an ADH2*2 allelo will increase the risk of SIDS in alcohol-exposed infants; and (4) to examine whether heavily alcohol-exposed neonates will exhibit alterations in autonomic nervous system behaviors similar to those described in SIDS victims, which are known to be regulated by the medullary serotonergic system, including arousal, cardiorespiratory reflex integration, and sleep/wake patterns. This research has the potential to improve our understanding of neurophysiological mechanisms involved in SIDS and to contribute to developing interventions for mothers and infants whose behaviors indicate that they are at risk for this adverse outcome.